Variant 20-2705581-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001395167.1(EBF4):c.142G>A(p.Val48Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,551,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

EBF4
NM_001395167.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.14

Variant links:

Genes affected

EBF4 (HGNC:29278): (EBF family member 4) EBF4 belongs to the conserved Olf/EBF family of helix-loop-helix transcription factors, members of which play important roles in neural development and B-cell maturation (Wang et al., 2002 [PubMed 12139918]).[supplied by OMIM, Mar 2008]

EBF4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32076782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBF4	NM_001395167.1 linkuse as main transcript	c.142G>A	p.Val48Met	missense_variant	2/17	ENST00000609451.6	NP_001382096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBF4	ENST00000609451.6 linkuse as main transcript	c.142G>A	p.Val48Met	missense_variant	2/17	5	NM_001395167.1	ENSP00000477023	P1	Q9BQW3-2
EBF4	ENST00000380648.9 linkuse as main transcript	c.130G>A	p.Val44Met	missense_variant	3/18	5		ENSP00000370022
EBF4	ENST00000497450.5 linkuse as main transcript	c.49G>A	p.Val17Met	missense_variant	3/5	3		ENSP00000501336
EBF4	ENST00000449079.7 linkuse as main transcript	c.130G>A	p.Val44Met	missense_variant, NMD_transcript_variant	3/18	2		ENSP00000405003

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

157716

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000895

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1399586

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

690322

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000839

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000158

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000124

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.130G>A (p.V44M) alteration is located in exon 3 (coding exon 3) of the EBF4 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the valine (V) at amino acid position 44 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.066

T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.3

.;.;M

MutationTaster

Benign

0.70

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.18

Sift

Uncertain

0.0050

D;.;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.47

MutPred

0.20

Gain of disorder (P = 0.058);.;.;

MVP

0.89

MPC

1.6

ClinPred

0.57

GERP RS

3.9

Varity_R

0.14

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over